Katoh Yuriko, Katoh Masaru
M and M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2005 Mar;26(3):841-5.
WNT family genes encode WNT family glycoproteins, while Frizzled (FZD) family genes encode seven-transmembrane-type receptors with extracellular WNT-binding domain and cytoplasmic Dishevelled-binding domain. WNT signaling pathway is implicated in carcinogenesis and embryogenesis. WNT1-WNT10B, WNT6-WNT10A, WNT3-WNT9B (WNT14B), WNT3A-WNT9A (WNT14) gene clusters exist within the human genome. Here, we identified and characterized rat Wnt1 and Wnt10b genes by using bioinformatics. Rat Wnt1 gene, consisting of four exons, encoded a 370-aa protein with signal peptide, 22 conserved Cys residues and four Asn-linked glycosylation sites. Rat Wnt10b gene, consisting of five exons, encoded a 389-aa protein with signal peptide, 24 conserved Cys residues and two Asn-linked glycosylation sites. Wnt1 and Wnt10b genes at rat chromosome 7q36 were clustered in head-to-head manner with an interval of about 10 kb within AC096835.4 or AC118760.4 genome sequences. Promoter region, exon 1 and 5'-part of intron 1 were conserved between rat and human Wnt1 orthologs. Intergenic conserved region (IGCR) was identified within the Wnt1-Wnt10b gene cluster. GC content of rat Wnt1-Wnt10b IGCR (nucleotide position 14962-15875 of AC096835.4 genome sequence) was 59.4%. Rat Wnt1-Wnt10b IGCR showed 92.5 and 74.4% nucleotide identity with mouse Wnt1-Wnt10b IGCR and human WNT1-WNT10B IGCR, respectively. Wnt1-Wnt10b IGCR was predicted as regulatory element rather than gene because cDNA or EST derived from Wnt1-Wnt10b IGCR was not identified. This is the first report on rat Wnt1 and Wnt10b genes as well as on Wnt1-Wnt10b IGCR.
WNT家族基因编码WNT家族糖蛋白,而卷曲蛋白(FZD)家族基因编码具有细胞外WNT结合结构域和细胞质散乱蛋白结合结构域的七跨膜型受体。WNT信号通路与肿瘤发生和胚胎发生有关。人类基因组中存在WNT1 - WNT10B、WNT6 - WNT10A、WNT3 - WNT9B(WNT14B)、WNT3A - WNT9A(WNT14)基因簇。在此,我们通过生物信息学方法鉴定并表征了大鼠Wnt1和Wnt10b基因。大鼠Wnt1基因由四个外显子组成,编码一种含信号肽、22个保守半胱氨酸残基和四个天冬酰胺连接糖基化位点的370个氨基酸的蛋白质。大鼠Wnt10b基因由五个外显子组成,编码一种含信号肽、24个保守半胱氨酸残基和两个天冬酰胺连接糖基化位点的389个氨基酸的蛋白质。大鼠7号染色体7q36上的Wnt1和Wnt10b基因在AC096835.4或AC118760.4基因组序列中以头对头的方式成簇排列,间隔约10 kb。大鼠和人类Wnt1直系同源基因之间的启动子区域、外显子1和内含子1的5'部分是保守的。在Wnt1 - Wnt10b基因簇内鉴定出基因间保守区域(IGCR)。大鼠Wnt1 - Wnt10b IGCR(AC096835.4基因组序列核苷酸位置14962 - 15875)的GC含量为59.4%。大鼠Wnt1 - Wnt10b IGCR与小鼠Wnt1 - Wnt10b IGCR和人类WNT1 - WNT10B IGCR的核苷酸同一性分别为92.5%和74.4%。由于未鉴定到源自Wnt1 - Wnt10b IGCR的cDNA或EST,Wnt1 - Wnt10b IGCR被预测为调控元件而非基因。这是关于大鼠Wnt1和Wnt10b基因以及Wnt1 - Wnt10b IGCR的首次报道。